TY - JOUR
T1 - Complete assignment of Ala, Ile, LeuProS, Met and ValProS methyl groups of the protruding domain from human norovirus GII.4 Saga
AU - Müller-Hermes, Christoph
AU - Creutznacher, Robert
AU - Mallagaray, Alvaro
N1 - Funding Information:
Open Access funding provided by Projekt DEAL. We thank the DFG (Deutsche Forschungsgemeinschaft) for funding this work as part of the ViroCarb research unit (FOR2327, DFG Pe494/12-2). The state of Schleswig-Holstein is thanked for supplying NMR infrastructure to the Institute of Chemistry and Metabolomics of the University of Lübeck (European Fonds for Regional Development, LPW-E/1.1.2/857).
Publisher Copyright:
© 2020, The Author(s).
Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2020/4/1
Y1 - 2020/4/1
N2 - Attachment of human noroviruses to histo blood group antigens (HBGAs) is thought to be essential for infection, although how this binding event promotes infection is unknown. Recent studies have shown that 60% of all GII.4 epidemic strains may undergo a spontaneous post-translational modification (PTM) in an amino acid located adjacent to the binding pocket for HBGAs. This transformation proceeds with an estimated half-life of 1–2 days under physiological conditions, dramatically affecting HBGA recognition. The surface-exposed position of this PTM and its sequence conservation suggests a relevant role in immune escape and host-cell recognition. As a first step towards the understanding of the biological implications of this PTM at atomic resolution, we report the complete assignment of methyl resonances of a MILProSVProSA methyl-labeled sample of a 72 kDa protruding domain from a GII.4 Saga human norovirus strain. Assignments were obtained from methyl–methyl NOESY experiments combined with site-directed mutagenesis and automated assignment. This data provides the basis for a detailed characterization of the PTM-driven modulation of immune recognition in human norovirus on a molecular level.
AB - Attachment of human noroviruses to histo blood group antigens (HBGAs) is thought to be essential for infection, although how this binding event promotes infection is unknown. Recent studies have shown that 60% of all GII.4 epidemic strains may undergo a spontaneous post-translational modification (PTM) in an amino acid located adjacent to the binding pocket for HBGAs. This transformation proceeds with an estimated half-life of 1–2 days under physiological conditions, dramatically affecting HBGA recognition. The surface-exposed position of this PTM and its sequence conservation suggests a relevant role in immune escape and host-cell recognition. As a first step towards the understanding of the biological implications of this PTM at atomic resolution, we report the complete assignment of methyl resonances of a MILProSVProSA methyl-labeled sample of a 72 kDa protruding domain from a GII.4 Saga human norovirus strain. Assignments were obtained from methyl–methyl NOESY experiments combined with site-directed mutagenesis and automated assignment. This data provides the basis for a detailed characterization of the PTM-driven modulation of immune recognition in human norovirus on a molecular level.
UR - http://www.scopus.com/inward/record.url?scp=85078410751&partnerID=8YFLogxK
U2 - 10.1007/s12104-020-09932-z
DO - 10.1007/s12104-020-09932-z
M3 - Journal articles
C2 - 31993958
AN - SCOPUS:85078410751
SN - 1874-2718
VL - 14
SP - 123
EP - 130
JO - Biomolecular NMR Assignments
JF - Biomolecular NMR Assignments
IS - 1
ER -